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Background Sickle cell disease (SCD) is a significant health concern, particularly due to the variability in disease severity and frequency of crisis episodes among patients. Accurate assessment of HbS concentrations is crucial for understanding the disease's progression and severity. This study aimed to assess and evaluate HbS concentrations in sickle cell patients and those experiencing sickle cell crisis using high-performance liquid chromatography (HPLC). The objectives included screening individuals for SCD, diagnosing the disease using Hb electrophoresis, estimating HbS concentration via HPLC, and comparing HbS concentration values between sickle cell patients and those in crisis. Methods An analytical study design was employed at Jawaharlal Nehru Medical College, Sawangi, Wardha, Maharashtra, involving 80 participants diagnosed with SCD. Data collection included clinical assessments, routine sickling tests, Hb electrophoresis, and HPLC for HbS concentration measurement. Descriptive and inferential statistics were utilized for data analysis, including chi-square tests, Mann-Whitney U tests, and regression analyses. Results Significant differences in HbS concentrations were observed between different patient groups. Individuals with the SS pattern exhibited higher HbS levels than those with the AS pattern (p = 0.001). Non-crisis patients had significantly higher mean HbS concentrations than crisis patients (p = 0.001). A moderate positive correlation (0.476, p = 0.001) was found between HbS concentrations and clinical outcomes. No significant differences in HbS concentrations were noted based on sex or age group. Longitudinal analysis revealed a significant increase in HbS levels over time (p = 0.001). Conclusion The study underscores the importance of HbS concentration measurement in understanding the severity and progression of SCD. HPLC proves to be a valuable tool in accurately estimating HbS levels, aiding in better clinical management of the disease.
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Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that has long been considered a concern only in the pediatric population. However, symptoms often sustain into adulthood and may require medication. For women with ADHD, this also means dealing with the disorder during the reproductive period. Medication safety during pregnancy and breastfeeding is a critical concern, and the potential transfer of ADHD medication to infants remains a topic of scientific interest. The quantification of ADHD medications in both maternal blood and breast milk are vital for understanding their pharmacokinetics and potential exposure risks for (nursing) infants. This review aims (1) to compile and critically assess existing research on the transfer of ADHD medications into breast milk and the potential implications for nursing infants and (2) to provide a comprehensive overview and discussion of the literature regarding the quantification of methylphenidate, amphetamine, atomoxetine, viloxazine, guanfacine, clonidine and bupropion in the blood, urine, oral fluid, and breast milk with liquid chromatography. A literature search was conducted using PubMed, Scopus, and Web of Science, to identify relevant articles published from January 2014 up to December 2023. We illustrate the lack of methods to simultaneously monitor multiple ADHD medications as well as the lack of developed methods for breast milk. Finally, we highlight the need for continued research to refine our understanding of medication transfer into breast milk and potential risks, and to develop clinical guidelines to support mothers with ADHD in making informed choices regarding medication use during pregnancy and lactation.
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Trastorno por Déficit de Atención con Hiperactividad , Lactancia Materna , Leche Humana , Humanos , Femenino , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Leche Humana/química , Embarazo , Cromatografía Liquida , Adulto , Metilfenidato/uso terapéuticoRESUMEN
Mefloquine, a widely used antimalarial agent, has spurred ongoing research into the development of derivatives with enhanced efficacy and reduced side effects. In this investigation, we synthesized two compounds containing N-allyl or N-tert-butylacetamid groups. A chiral liquid chromatography with polysaccharide chiral stationary phase was utilized to separate the enantiomers of both derivatives. We employed spectroscopic chiroptical and non-polarizable methods such as electronic and vibrational circular dichroism, infrared absorption and ultraviolet spectroscopies. Combined with density functional theory calculations, the stable conformers were found in solution and their spectra were subsequently simulated. We elucidated the three-dimensional structure of the enantiomerically pure compounds and assigned the absolute configuration of all prepared derivatives using both experimental and simulated spectra.
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Polylactic acid (PLA) straws hold eco-friendly potential; however, residual diisocyanates used to enhance the mechanical strength can generate carcinogenic primary aromatic amines (PAAs), posing health risks. Herein, we present a rapid, comprehensive strategy to detecting PAAs in 18 brands of food-grade PLA straws and assessing their migration into diverse food simulants. Surface-enhanced Raman spectroscopy was conducted to rapidly screen straws for PAAs. Subsequently, qualitative determination of migrating PAAs into various food simulants (4 % acetic acid, 10 % ethanol, 50 % ethanol) occurred at 70 °C for 2 h using liquid chromatography-mass spectrometry. Three PAAs including 4,4'-methylenedianiline, 2,4'-methylenedianiline, and 2,4-diaminotoluene were detected in all straws. Specifically, 2,4-diaminotoluene in 50 % ethanol exceeded specific migration limit of 2 µg/kg, raising safety concerns. Notably, PAAs migration to 10 % and 50 % ethanol surpassed that to 4 % acetic acid within a short 2-hour period. Moreover, PLA straws underwent varying degrees of shape changes before and after migration. Straws with poly(butylene succinate) resisted deformation compared to those without, indicating enhanced heat resistance, while poly(butyleneadipate-co-terephthalate) improved hydrolysis resistance. Importantly, swelling study unveiled swelling effect wasn't the primary factor contributing to the increased PAAs migration in ethanol food simulant, as there was no significant disparity in swelling degrees across different food simulants. FT-IR and DSC analysis revealed higher PAAs content in 50 % ethanol were due to highly concentrated polar ethanol disrupting hydrogen bonds and van der Waal forces holding PLA molecules together. Overall, minimizing contact between PLA straws and alcoholic foods is crucial to avoid potential safety risks posed by PAAs.
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Nucleic acid duplexes are typically analyzed in non-denaturing conditions. Melting temperature (Tm) is the property used to measure duplex stability; however, it is not known how the chromatographic conditions and mobile phase composition affect the duplex stability. We employed differential scanning calorimetry (DSC) method to measure the melting temperature of chemically modified silencing RNA duplex (21 base pairs, 0.15 mM duplex concentration) in mobile phases commonly used in reversed-phase, ion-pair reversed-phase, size exclusion and hydrophilic interaction chromatography. We investigated mobile phases consisting of ammonium acetate, alkylammonium ion-pairing reagents, alkali-ion chlorides, magnesium chloride, and additives including methanol, ethanol, acetonitrile and hexafluoroisopropanol. Increasing buffer concentration enhanced the duplex stability (Tm was 67.1 - 78.2 °C for 10-100 mM [Na+] concentration). The melting temperature decreases with the increase in cation size (70.2 °C in 10 mM [Li+], 68.1 °C in 10 mM [NH4+], 65.6 °C in 10 mM [Cs+], and 56.6 °C in 10 mM [triethylammonium+] solutions). Inclusion of 20 % of organic solvent in buffer reduced the melting temperature by 1-3 °C, and denaturation power increases in the order MeOH
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Introduction: Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation. Methods: CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels. Results: Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features. Discussion: This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.
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Biomarcadores de Tumor , Neoplasias Encefálicas , Proteómica , Humanos , Proteómica/métodos , Biomarcadores de Tumor/líquido cefalorraquídeo , Neoplasias Encefálicas/líquido cefalorraquídeo , Neoplasias Encefálicas/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Diagnóstico Diferencial , Adulto , Linfoma no Hodgkin/líquido cefalorraquídeo , Linfoma no Hodgkin/diagnósticoRESUMEN
Formaldehyde is naturally present as a product of common metabolism in a diverse range of foods, including meat, fish, vegetables, and processed foods, and can also be introduced to food unintentionally due to its ubiquity in the environment. There has been increased interest in dietary exposure to formaldehyde because of its adverse health effects via multiple sources. The aim of this study was to evaluate the formaldehyde levels in various agricultural products and conduct a deterministic exposure assessment for the South Korean population. Formaldehyde levels were measured using high-performance liquid chromatography, with the samples extracted using water and then derivatized with 2,4-dinitrophenylhydrazine. The levels of formaldehyde were found to range from 0.006 to 25.6 µg/g in agricultural food products (n = 480). For the deterministic exposure assessment, multiple sources for point estimation were employed, with consumption data taken from the 2017 Korean Nutrition Survey. The mean daily formaldehyde exposure per each person was 127.5 µg for the South Korean, constituting approximately 1.4% of the tolerable daily intake (TDI). The hazard index (the ratio of the entire formaldehyde exposure to the TDI) normally fell within the range from 0.01 to 0.22 based on assumptions employed in the deterministic estimation of dietary intake. Based on these estimates, the exposure of the general South Korean to formaldehyde was considered to be safe. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01547-7.
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Vitamin B1 (thiamine pyrophosphate (TPP)) and B6 (pyridoxal 5'- phosphate (PLP)) deficiencies pose significant health risks. The current measurement method employs High-Performance Liquid Chromatography (HPLC), though, Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) is considered a more sensitive and selective analytical method. However, there is a lack of LC-MS/MS-based reference intervals. Moreover, none of the existing reference intervals are established in Danish populations. Therefore, the aim of this study was to establish a reference interval for whole blood concentrations of TPP and PLP in Danish blood donors using LC-MS/MS. Blood samples were collected from healthy Danish blood donors and analysed using the reagent kit, MassChrom® Vitamins B1 and B6 in whole blood (Chromsystems Instruments & Chemicals GmbH, Munich, Germany) for quantitative determination of both TPP and PLP concentration in whole blood, using LC-MS/MS. Reference intervals were determined with non-parametric methods as the 2.5th and 97.5th percentile and presented with 90% confidence intervals (CI). In total 120 blood donors were included. The concentrations of TTP or PLP were not statistically different between sexes just as age did not affect the concentrations, hence, combined reference intervals were employed. The resulting reference intervals are: TPP, nmol/L: 101.0 (90% CI: 96.4-108.5) - 189.0 (90% CI: 184.7-192.0) and PLP, nmol/L: 64.0 (90% CI: 60.9-66.7) - 211.8 (90% CI: 168.3-231.0). In conclusion, reference intervals for whole blood TTP and PLP in a healthy Danish population were established based on a LC-MS/MS method. Furthermore, the reference intervals were not affected by age or sex.
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Reliable analytical methods are the basis for the elucidation of phenolic compounds in foods. This study aimed to optimize and validate a method for determining 42 phenolics using reverse-phase (RP) high-performance liquid chromatography (HPLC) coupled to diode-array-detector-DAD. The performance of two RP columns was evaluated. The 150x4.6 mm 3-µm column showed superior separation quality, whereas 35 of the 42 phenolics showed a separation resolution ≥1.5. The method's linearity, precision (coefficient variation< 3.09%), recovery (87.5-103.2%), specificity, limits of detection (0.04-0.25 mg/L), and quantification (0.06-0.25 mg/L) had acceptable ranges. Thirty phenolics were quantified in Citrus peels, mainly flavanones, flavanols, flavonols, and phenolic acids, highlighting the high values of hesperidin (535-35070 mg/kg) and naringin (26-36466 mg/kg). Lemon peels named 'Lisboa,' 'Thaiti,' 'Thaiti-2000', and 'Thaiti-2001' presented the main phenolics associated with antioxidant capacity. The presented method was robust for determining 42 phenolic compounds, offering a new approach for bioactive compound quantification in food matrices.
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Cholesteryl esters (CE) are sterols comprising various fatty acyl chains attached to a cholesterol hydroxyl moiety. CEs are often considered plasma biomarkers of liver function; however, their absolute concentrations in the plasma of Japanese preadolescents have not been well explored. This study aimed to determine the plasma CE levels in Japanese preadolescents of different sexes, ages, and body weights living in Hokkaido, Japan using targeted liquid chromatography/tandem mass spectrometry. The analysis was performed on the non-fasting plasma of preadolescents aged 9-12â¯years (nâ¯=â¯339 healthy volunteers; 178 boys and 161 girls) from Sapporo, Hokkaido, Japan. The analysis results showed that the total CE levels in boys and girls were 871⯱â¯153 and 862⯱â¯96â¯pmol/µL, respectively. CE 18:2 (41⯱â¯2.9â¯%) was found to be the most abundant species followed by CE 18:1 (16⯱â¯1.5â¯%) and CE 16:0 (13⯱â¯1.1â¯%). The ω-3 fatty acid-containing CEs such as CE 18:3 and CE 20:5 were significantly lower in girls than in boys. Despite the different ages, CEs were tightly regulated in the plasma of children's, and the total CEs ranged between 844 and 906â¯pmol/µL in boys and 824 and 875â¯pmol/µL in girls. The participants were further classified into three groups based on their body mass index underweight (nâ¯=â¯237), normal weight (nâ¯=â¯94), and overweight (nâ¯=â¯8). Most of the quantified CEs were accumulated in the overweight group. Interestingly, CE 18:3 was significantly upregulated in the overweight group compared to that in the normal range, and the area under the receiver operating characteristic curve was 0.73, suggesting that it could be a possible marker for obesity. This study marks the initial investigation of absolute CE levels in the plasma of children and can help elucidate the relationship between CEs and childhood obesity.
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PURPOSE: The study aims to leverage the capabilities of Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry (LC-MRM), a key technique in quantifying therapeutic proteins in pharmacokinetic studies. The focus is on demonstrating an enrichment method using ProteoMiner beads, which can be integrated with LC-MRM to detect low-abundance biotherapeutics in serum, such as monoclonal antibodies and gene therapy products. METHODS: The ProteoMiner enrichment method was employed and integrated with LC-MRM. The lower limit of quantification of serum drug substance concentrations was compared with that achievable with immuno-enrichment. The method used commercially available reagents, eliminating the need for assay-specific antibodies and reducing potential bias and development time. RESULTS: The ProteoMiner enrichment method showed comparable performance to immuno-enrichment, meeting traditional assay requirements in terms of precision, accuracy, and specificity. CONCLUSIONS: The ProteoMiner enrichment method, when combined with LC-MRM, offers a reliable and efficient alternative to immuno-enrichment for detecting and quantifying low-abundance biotherapeutics in serum. This approach, which uses commercially available reagents, can eliminate the bias and time associated with the development of assay-specific antibodies. It holds significant potential for accelerating pharmacokinetic analysis in both early and late stages of pharmaceutical development.
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Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS) is a widely utilized technique for in vivo pharmaceutical analysis. Ionization interference within electrospray ion source, occurring between drugs and metabolites, can lead to signal variations, potentially compromising quantitative accuracy. Currently, method validation often overlooks this type of signal interference, which may result in systematic errors in quantitative results without matrix-matched calibration. In this study, we conducted an investigation using ten different groups of drugs and their corresponding metabolites across three LC-ESI-MS systems to assess the prevalence of signal interference. Such interferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites, thereby altering the relationship between analyte response and concentration for quantification. Finally, we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods: chromatographic separation, dilution, and stable labeled isotope internal standards correction. The above strategies were integrated into the method establishment process to improve quantitative accuracy.
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The amino acid position within a histone sequence and the chemical nature of post-translational modifications (PTMs) are essential for elucidating the "Histone Code". Previous work has shown that PTMs induce specific biological responses and are good candidates as biomarkers for diagnostics. Here, we evaluate the analytical advantages of trapped ion mobility (TIMS) with parallel accumulation-serial fragmentation (PASEF) and tandem mass spectrometry (MS/MS) for bottom-up proteomics of model cancer cells. The study also considered the use of nanoliquid chromatography (LC) and traditional methods: LC-TIMS-PASEF-ToF MS/MS vs nLC-TIMS-PASEF-ToF MS/MS vs nLC-MS/MS. The addition of TIMS and PASEF-MS/MS increased the number of detected peptides due to the added separation dimension. All three methods showed high reproducibility and low RSD in the MS domain (<5 ppm). While the LC, nLC and TIMS separations showed small RSD across samples, the accurate mobility (1/K0) measurements (<0.6% RSD) increased the confidence of peptide assignments. Trends were observed in the retention time and mobility concerning the number and type of PTMs (e.g., ac, me1-3) and their corresponding unmodified, propionylated peptide that aided in peptide assignment. Mobility separation permitted the annotation of coeluting structural and positional isomers and compared with nLC-MS/MS showed several advantages due to reduced chemical noise.
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Background and aims: Aberrations in the immunoglobulin heavy chain (IgH) locus are associated with poor prognosis in pediatric precursor B-cell acute lymphoblastic leukemia (BCP-ALL) patients. The primary objective of this pilot study is to enhance our understanding of the IgH phenotype by exploring the intracellular chiral metabolome. Materials and methods: Leukemia cells were isolated from the bone marrow of BCP-ALL pediatric patients at diagnosis. The samples' metabolome and transcriptome were characterized using untargeted chiral metabolomic and next-generation sequencing transcriptomic analyses. Results: For the first time D- amino acids were identified in the leukemic cells' intracellular metabolome from the bone marrow niche. Chiral metabolic signatures at diagnosis was indicative of a resistant phenotype. Through integrated network analysis and Pearson correlation, confirmation was obtained regarding the association of the IgH phenotype with several genes linked to poor prognosis. Conclusion: The findings of this study have contributed to the understanding that the chiral metabolome plays a role in the poor prognosis observed in an exceptionally rare patient cohort. The findings include elevated D-amino acid incorporation in the IgH group, the emergence of several unknown, potentially enantiomeric, metabolites, and insights into metabolic pathways that all warrant further exploration.
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Reversed-phase liquid chromatography (RPLC) represents an effective separation method, and is widely employed as the second dimension in most 2D-LC systems. Nevertheless, the solvent effect of the eluent from the first dimension on RPLC presents a challenge to the online coupling of RPLC with other separation modes, particularly normal phase liquid chromatography (NPLC). To address this issue, a comprehensive understanding of the solvent effect is essential. Following a comprehensive investigation into the influence of diverse solvents on RPLC separations, it was observed that alkane solvents, such as n-hexane, exhibited a pronounced tendency to be retained during RPLC separations. Such solvents do not affect the analysis of samples with weaker retention abilities than themselves, even when a large injection volume is used. The solvent effect was thus reduced by employing n-hexane-based solvent dilution. Leveraging the markedly enhanced solvent tolerance and extensive injection volume in RPLC, a versatile integration of the NPLC and RPLC was devised, necessitating merely a purge pump and a 10 port 2 position valve in conjunction with two sample loops. The novel 2D-LC system was then deployed for the analysis of propolis, a naturally occurring complex sample, and demonstrated remarkable separation efficiency.
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The pharmaceutical industry is rapidly advancing toward new drug modalities, necessitating the development of advanced analytical strategies for effective, meaningful, and reliable assays. Hydrophilic Interaction Chromatography (HILIC) is a powerful technique for the analysis of polar analytes. Despite being a well-established technique, HILIC method development can be laborious owing to the multiple factors that affect the separation mechanism, such as the selection of stationary phase chemistry, mobile phase eluents, and optimization of column equilibration time. Herein, we introduce a new automated multicolumn and multi-eluent screening workflow that streamlines the development of new HILIC assays, circumventing the existing tedious 'hit-or-miss' approach. A total of 12 complementary columns packed with sub-2 µm fully porous and 2.7 µm superficially porous particles operated on readily available ultra-high pressure liquid chromatography (UHPLC) instrumentation across a diverse set of commercially available polar stationary phases were investigated. Different mobile phases with pH ranging from pH 3 to 9 were evaluated using different organic modifiers. The gradient and column re-equilibration were judiciously set to ensure a reliable assay screening framework that indicates promising conditions for subsequent method optimization to achieve resolution of challenging mixtures. This UHPLC screening system is coupled with a diode array and charged aerosol detectors (DAD, CAD and mass spectrometry) to ensure versatile detection for a variety of compounds. This fast-screening platform lays the foundation for a convenient generic workflow, accelerating the pace of HILIC method development and transfer across both academic and industrial sectors.
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In this work, a composite hydrogel material consisting of chitosan-based composite hydrogel was prepared by a simple and rapid synthetic method and will be named three-dimensional (3D)-IL-COF-1@CS hydrogel. Possessing a stable 3D network structure and outstanding hydrophilicity, the novel hydrogel is capable of capturing glycopeptides. The 3D-IL-COF-1@CS hydrogel showed good sensitivity (0.1 fmol/µL) and selectivity (1:2000). In addition, 19 glycopeptides were captured in standard samples. In the analysis of human serum, 148 glycopeptides assigned to 72 glycoproteins were assayed in the serum of normal individuals, and 245 glycopeptides corresponding to 100 glycoproteins were found in the serum of colorectal cancer (CRC) patients. More importantly, several functional programs based on Gene Ontology analysis supported molecular biological processes that may be relevant to the pathogenesis of CRC, including aging, fibrinogen complex, and arylesterase activity. The low cost, simplicity, rapid synthesis, and good enrichment performance have a great future in glycoproteomics analysis and related diseases.
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Neoplasias Colorrectales , Glicopéptidos , Interacciones Hidrofóbicas e Hidrofílicas , Humanos , Neoplasias Colorrectales/sangre , Glicopéptidos/sangre , Glicopéptidos/química , Hidrogeles/química , Polímeros/química , Quitosano/químicaRESUMEN
OBJECTIVES: To screen biomarkers for forensic identification of acute myocardial infarction (AMI) by non-targeted metabolomic studies on changes of urine metabolites in rats with AMI. METHODS: The rat models of the sham surgery group, AMI group and hyperlipidemia + acute myocardial infarction (HAMI) group were established. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the changes of urine metabolic spectrometry in AMI rats. Principal component analysis, partial least squares-discriminant analysis, and orthogonal partial least squares-discriminant analysis were used to screen differential metabolites. The MetaboAnalyst database was used to analyze the metabolic pathway enrichment and access the predictive ability of differential metabolites. RESULTS: A total of 40 and 61 differential metabolites associated with AMI and HAMI were screened, respectively. Among them, 22 metabolites were common in both rat models. These small metabolites were mainly concentrated in the niacin and nicotinamide metabolic pathways. Within the 95% confidence interval, the area under the curve (AUC) values of receiver operator characteristic curve for N8-acetylspermidine, 3-methylhistamine, and thymine were greater than 0.95. CONCLUSIONS: N8-acetylspermidine, 3-methylhistamine, and thymine can be used as potential biomarkers for AMI diagnosis, and abnormal metabolism in niacin and nicotinamide may be the main causes of AMI. This study can provide reference for the mechanism and causes of AMI identification.
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Biomarcadores , Modelos Animales de Enfermedad , Metabolómica , Infarto del Miocardio , Animales , Infarto del Miocardio/metabolismo , Infarto del Miocardio/orina , Ratas , Metabolómica/métodos , Masculino , Biomarcadores/orina , Biomarcadores/metabolismo , Cromatografía Líquida de Alta Presión , Ratas Sprague-Dawley , Análisis de Componente Principal , Análisis Discriminante , Espectrometría de Masas/métodos , Niacina/metabolismo , Niacina/orina , Hiperlipidemias/metabolismo , Niacinamida/orina , Niacinamida/metabolismo , Niacinamida/análogos & derivados , Redes y Vías Metabólicas , Curva ROC , Análisis de los Mínimos Cuadrados , Medicina Legal/métodos , MetabolomaRESUMEN
Piperazines are a class of new psychoactive substances with hallucinogenic effects that affect the central nervous system by affecting the level of monoamine neurotransmitters. Abuse of piperazines will produce stimulating and hallucinogenic effects, accompanied by headache, dizziness, anxiety, insomnia, vomiting, chest pain, tachycardia, hypertension and other adverse reactions, and may even cause cardiovascular diseases and multiple organ failure and lead to death, seriously affecting human physical and mental health and public safety. The abuse of new psychoactive substance piperazines has attracted extensive attention from the international community. The study of its pharmacological toxicology and analytical methods has become a research hotspot in the field of forensic medicine. This paper reviews the in vivo processes, sample treatment and analytical methods of existing piperazines, in order to provide reference for forensic identification.
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Piperazinas , Psicotrópicos , Detección de Abuso de Sustancias , Humanos , Piperazinas/análisis , Psicotrópicos/análisis , Detección de Abuso de Sustancias/métodos , Medicina Legal/métodos , Toxicología Forense/métodos , Alucinógenos/análisis , Trastornos Relacionados con Sustancias/diagnósticoRESUMEN
Perfluorinated and polyfluoroalkyl substances (PFASs) are compounds characterized by at least one perfluorinated carbon atom in an alkyl chain linked to side-chain groups. Owing to their unique chemical properties, these compounds are widely used in industrial production and daily life. However, owing to anthropogenic activities, sewage discharge, surface runoff, and atmospheric deposition, PFASs have gradually infiltrated the environment and aquatic resources. With their gradual accumulation in environmental waters, PFASs have been detected in fishes and several fish-feeding species, suggesting that they are bioconcentrated and even amplified in aquatic organisms. PFASs exhibit high intestinal absorption efficiencies, and they bioaccumulate at higher trophic levels in the food chain. They can be bioconcentrated in the human body via food (e. g., fish) and thus threaten human health. Therefore, establishing an efficient analytical technique for use in analyzing PFASs in typical fish samples and providing technical support for the safety regulation and risk assessment of fish products is necessary. In this study, by combining solvent extraction and magnetic dispersion-solid phase extraction (d-SPE), an improved QuEChERS method with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the determination of 13 PFASs in fish samples. Fe3O4-TiO2 can be used as an ideal adsorbent in the removal of sample matrix interference and a separation medium for the rapid encapsulation of other solids to be isolated from the solution. Based on the matrix characteristics of the fish products and structural properties of the target PFASs, Fe3O4-TiO2 and N-propyl ethylenediamine (PSA) were employed as adsorbents in dispersive purification. The internal standard method was used in the quantitative analyses of the PFASs. To optimize the sample pretreatment conditions of analyzing PFASs, the selection of the extraction solvent and amounts of Fe3O4-TiO2 and PSA were optimized. Several PFASs contain acidic groups that are non-dissociated in acidic environments, thus favoring their entry into the organic phase. In addition, acidified acetonitrile can denature and precipitate the proteins within the sample matrix, facilitating their removal. Finally, 2% formic acid acetonitrile was used as the extraction solvent, and 20 mg Fe3O4-TiO2, 20 mg PSA and 120 mg anhydrous MgSO4 were used as purification adsorbents. Under the optimized conditions, the developed method exhibited an excellent linearity (R≥0.9973) in the range of 0.01-50 µg/L, and the limits of detection (LODs) and quantification (LOQs) ranged from 0.001-0.023 and 0.003-0.078 µg/L, respectively. The recoveries of the 13 PFASs at low, medium, and high spiked levels (0.5, 10, and 100 µg/kg) were 78.1%-118%, with the intra- and inter-day precisions of 0.2%-11.1% and 0.8%-8.7%, respectively. This method was applied in analyzing real samples, and PFASs including perfluorooctanesulfonic acid, perfluorooctanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotridecanoic acid, were detected in all 11 samples evaluated. This method is simple, sensitive, and suitable for use in analyzing PFASs in fish samples.